tbuckley/cabot-search huggingface dataset:
Vaccination with a structure-based stabilized version of malarial antigen Pfs48/45 elicits ultra-potent transmission-blocking antibody responses
Authors: Brandon McLeod, Moustafa T. Mabrouk, Kazutoyo Miura, Rashmi Ravichandran, Sally Kephart, Sophia Hailemariam, Thao P. Pham, Anthony Semesi, Iga Kucharska, Prasun Kundu, Wei-Chiao Huang, Max Johnson, Alyssa Blackstone, Deleah Pettie, Michael Murphy, John C. Kraft, Elizabeth M. Leaf, Yang Jiao, Marga van de Vegte-Bolmer, Geert-Jan van Gemert, Jordache Ramjith, C. Richter King, Randall S. MacGill, Yimin Wu, Kelly K. Lee, Matthijs M. Jore, Neil P. King, Jonathan F. Lovell, Jean-Philippe Julien
Journal: Immunity (2022)

Malaria transmission-blocking vaccines (TBVs) aim to elicit human antibodies that inhibit sporogonic development of Plasmodium falciparum in mosquitoes, thereby preventing onward transmission. Pfs48/45 is a leading clinical TBV candidate antigen and is recognized by the most potent transmission-blocking monoclonal antibody (mAb) yet described; still, clinical development of Pfs48/45 antigens has been hindered, largely by its poor biochemical characteristics. Here, we used structure-based computational approaches to design Pfs48/45 antigens stabilized in the conformation recognized by the most potently inhibitory mAb, achieving >25°C higher thermostability compared with the wild-type protein. Antibodies elicited in mice immunized with these engineered antigens displayed on liposome-based or protein nanoparticle-based vaccine platforms exhibited 1–2 orders of magnitude superior transmission-reducing activity, compared with immunogens bearing the wild-type antigen, driven by improved antibody quality. Our data provide the founding principles for using molecular stabilization solely from antibody structure-function information to drive improved immune responses against a parasitic vaccine target.
The mitochondrial calcium uniporter engages UCP1 to form a thermoporter that promotes thermogenesis
Authors: Kaili Xue, Dongmei Wu, Yushuang Wang, Yiheng Zhao, Hongyu Shen, Jingfei Yao, Xun Huang, Xinmeng Li, Zhao Zhou, Zihao Wang, Yifu Qiu
Journal: Cell Metabolism (2022)
Neoadjuvant immunotherapy of locoregionally advanced solid tumors
Authors: Ahmad A Tarhini, Jennifer R Eads, Kathleen N Moore, Valerie Tatard-Leitman, John Wright, Patrick M Forde, Robert L Ferris
Journal: Journal for ImmunoTherapy of Cancer (2022)

Definitive management of locoregionally advanced solid tumors presents a major challenge and often consists of a combination of surgical, radiotherapeutic and systemic therapy approaches. Upfront surgical treatment with or without adjuvant radiotherapy carries the risks of significant morbidities and potential complications that could be lasting. In addition, these patients continue to have a high risk of local or distant disease relapse despite the use of standard adjuvant therapy. Preoperative neoadjuvant systemic therapy has the potential to significantly improve clinical outcomes, particularly in this era of expanding immunotherapeutic agents that have transformed the care of patients with metastatic/unresectable malignancies. Tremendous progress has been made with neoadjuvant immunotherapy in the treatment of several locoregionally advanced resectable solid tumors leading to ongoing phase 3 trials and change in clinical practice. The promise of neoadjuvant immunotherapy has been supported by the high pathologic tumor response rates in early trials as well as the durability of these responses making cure a more achievable potential outcome compared with other forms of systemic therapy. Furthermore, neoadjuvant studies allow the assessment of radiologic and pathological responses and the access to biospecimens before and during systemic therapy. Pathological responses may guide future treatment decisions, and biospecimens allow the conduct of mechanistic and biomarker studies that may guide future drug development. On behalf of the National Cancer Institute Early Drug Development Neoadjuvant Immunotherapy Working Group, this article summarizes the current state of neoadjuvant immunotherapy of solid tumors focusing primarily on locoregionally advanced melanoma, gynecologic malignancies, gastrointestinal malignancies, non-small cell lung cancer and head and neck cancer including recent advances and our expert recommendations related to future neoadjuvant trial designs and associated clinical and translational research questions.
Integrated Forecasts Based on Public Health Surveillance and Meteorological Data Predict West Nile Virus in a High-Risk Region of North America
Authors: Michael C. Wimberly, Justin K. Davis, Michael B. Hildreth, Joshua L. Clayton
Journal: Environmental Health Perspectives (2022)

West Nile virus (WNV), a global arbovirus, is the most prevalent mosquito-transmitted infection in the United States. Forecasts of WNV risk during the upcoming transmission season could provide the basis for targeted mosquito control and disease prevention efforts. We developed the Arbovirus Mapping and Prediction (ArboMAP) WNV forecasting system and used it in South Dakota from 2016 to 2019. This study reports a post hoc forecast validation and model comparison.Our objective was to validate historical predictions of WNV cases with independent data that were not used for model calibration. We tested the hypothesis that predictive models based on mosquito surveillance data combined with meteorological variables were more accurate than models based on mosquito or meteorological data alone.The ArboMAP system incorporated models that predicted the weekly probability of observing one or more human WNV cases in each county. We compared alternative models with different predictors including a) a baseline model based only on historical WNV cases, b) mosquito models based on seasonal patterns of infection rates, c) environmental models based on lagged meteorological variables, including temperature and vapor pressure deficit, d) combined models with mosquito infection rates and lagged meteorological variables, and e) ensembles of two or more combined models. During the WNV season, models were calibrated using data from previous years and weekly predictions were made using data from the current year. Forecasts were compared with observed cases to calculate the area under the receiver operating characteristic curve (AUC) and other metrics of spatial and temporal prediction error.Mosquito and environmental models outperformed the baseline model that included county-level averages and seasonal trends of WNV cases. Combined models were more accurate than models based only on meteorological or mosquito infection variables. The most accurate model was a simple ensemble mean of the two best combined models. Forecast accuracy increased rapidly from early June through early July and was stable thereafter, with a maximum AUC of 0.85. The model predictions captured the seasonal pattern of WNV as well as year-to-year variation in case numbers and the geographic pattern of cases.The predictions reached maximum accuracy early enough in the WNV season to allow public health responses before the peak of human cases in August. This early warning is necessary because other indicators of WNV risk, including early reports of human cases and mosquito abundance, are poor predictors of case numbers later in the season. https://doi.org/10.1289/EHP10287.
Hyperparathyroidism Caused by Coexisting Parathyroid Hyperplasia and Unilateral Bifocal Parathyroid Carcinoma
Authors: Wei Liu, Jian-Min Huang, Mei-Chao Guan, Peng Xie
Journal: Clinical Nuclear Medicine (2022)

The coexistence of parathyroid hyperplasia and carcinoma is uncommon. Here we report findings of 99m Tc-sestamibi SPECT/CT study in a case of unilateral bifocal parathyroid carcinoma coexisting with parathyroid hyperplasia in a 49-year-old man. The images showed 4 foci of elevated activity around the thyroid. Histopathology confirmed the 2 lesions of the left side as parathyroid hyperplasia and the other 2 lesions of the right side as parathyroid carcinoma.
Corrigendum to “Tumor volume predicts local recurrence in early rectal cancer treated with radical resection: A retrospective observational study of 270 patients”. [Int. J. Surg. 49 January 2018 Pages 68–73]
Authors: Yanhui Jiang, Kaiyun You, Xingsheng Qiu, Zhuofei Bi, Huaqian Mo, Liting Li, Yimin Liu
Journal: International Journal of Surgery (2022)
The associations between modifiable risk factors and nonalcoholic fatty liver disease: A comprehensive Mendelian randomization study
Authors: Jiarong Xie, Hangkai Huang, Zhening Liu, Youming Li, Chaohui Yu, Lei Xu, Chengfu Xu
Journal: Hepatology (2022)

Background and Aims: Early identification of modifiable risk factors is essential for the prevention of nonalcoholic fatty liver disease (NAFLD). We aimed to systematically explore the relationships between genetically predicted modifiable risk factors and NAFLD. Approach and Results: We applied univariable and multivariable Mendelian randomization analyses to explore the relationships between 35 modifiable risk factors and NAFLD. We also evaluated the combined results in three independent large genome‐wide association studies. Genetically predicted alcohol frequency, elevated serum levels of liver enzymes, triglycerides, C‐reactive protein, and obesity traits, including body mass index, waist circumference, and body fat mass, were associated with increased risks of NAFLD (all with p &lt; 0.05). Poor physical condition had a suggestive increased risk for NAFLD (odds ratio [OR] = 2.63, p = 0.042). Genetically instrumented type 2 diabetes (T2DM), hypothyroidism, and hypertension all increased the risk for NAFLD, and the ORs (95% confidence interval) were 1.508 (1.20–1.90), 13.08 (1.53–111.65), and 3.11 (1.33–7.31) for a 1‐U increase in log‐transformed odds, respectively. The positive associations of T2DM and hypertension with NAFLD remained significant in multivariable analyses. The combined results from the discovery and two replication datasets further confirmed that alcohol frequency, elevated serum liver enzymes, poor physical condition, obesity traits, T2DM, and hypertension significantly increase the risk of NAFLD, whereas higher education and high‐density lipoprotein cholesterol (HDL‐cholesterol) could lower NAFLD risk. Conclusions: Genetically predicted alcohol frequency, elevated serum liver enzymes, poor physical condition, obesity traits, T2DM, and hypertension were associated with an increased risk of NAFLD, whereas higher education and HDL‐cholesterol were associated with a decreased risk of NAFLD.
The Evolving Epidemiology of Oral Cavity and Oropharyngeal Cancers
Authors: Anil K. Chaturvedi, Neal D. Freedman, Christian C. Abnet
Journal: Cancer Research (2022)

In 1988, Blot and colleagues reported results from a U.S. case–control study of oral cavity or pharyngeal (oropharyngeal and hypopharyngeal) cancers, with results showing independent associations of smoking and alcohol with increased risk, multiplicative interaction effects between smoking and alcohol, and that nearly three-quarters of these cancers are attributable to smoking and alcohol. The report by Blot and colleagues represents a landmark in oropharyngeal cancer epidemiology. This study, the largest at the time, introduced several novel concepts in oropharyngeal cancer epidemiology that remain relevant today—etiologic heterogeneity, statistical interaction effects, adjusted attributable fractions, and disparities by sex and race/ethnicity. Perhaps the most significant recognition in the field since 1988 is the etiologic association of human papillomavirus (HPV, primarily HPV16) with cancers arising in the oropharynx. Today, more than 80% of oropharyngeal cancers in the United States are caused by HPV while only approximately 3% of oral cavity cancers are caused by HPV. This etiologic heterogeneity across head and cancer subsites revealed by HPV is manifest at the genetic/genomic, epidemiologic, and clinical levels. Tobacco and alcohol remain the major etiologic factors for oral cavity cancers while HPV is the major cause of oropharyngeal cancers. Thus, tobacco and alcohol control and prophylactic HPV vaccination remain the most promising prevention tools for oral cavity and oropharyngeal cancers at this time. Importantly, the ever-emerging alternative tobacco products, such as smokeless tobacco/snus, hookah and water pipes, e-cigarettes, flavored cigars and cigarillos, and oral dissolvable products, represent a key public health concern and the carcinogenic effects of these products remains an active area of investigation. See related article by Blot and colleagues, Cancer Res 1988;48:3282–7
Highlights from Recent Cancer Literature
Journal: Cancer Research (2022)

Super-Enhancer Mutations Drive LymphomagenesisAlthough recurrent genetic alterations in coding regions have been well characterized in diffuse large B-cell lymphoma (DLBCL), these alterations alone appear to be insufficient to drive lymphomagenesis.Bal and colleagues have now uncovered recurrent mutations in noncoding regions in super-enhancers, leading to loss of transcriptional repression of oncogenes, resulting in tumorigenesis.These recurrent mutations share an activation-induced cytidine deaminase signature implicating activation-induced cytidine deaminase as the mutational driver.CRISPR-Cas9-mediated reversion of these mutations led to a significant decrease in oncogene expression and prevented proliferation and survival of DLBCL cell lines.
i-CRISPR: a personalized cancer therapy strategy through cutting cancer-specific mutations
Authors: Junfeng Jiang, Yuanyuan Chen, Li Zhang, Qishu Jin, Liujun Wang, Sha Xu, Kexin Chen, Li Li, Tao Zeng, Xingfei Fan, Tingting Liu, Jiaxi Li, Jinjiang Wang, Chaofeng Han, Fu Gao, Yanyong Yang, Yue Wang
Journal: Molecular Cancer (2022)

Abstract Developing a strategy to specifically kill cancer cells without inducing obvious damage to normal cells may be of great clinical significance for cancer treatment. In the present study, we developed a new precise personalized strategy named "i-CRISPR" for cancer treatment through adding DNA damage repair inhibitors(i) and inducing cancer cell-specific DNA double strand breaks by CRISPR. Through in vitro and in vivo experiments, we confirmed the efficacy of this strategy in multiple cancer models and revealed the mechanism of cell death. Our strategy might provide a novel concept for precise cancer therapy.
COVID-19 pandemic-associated chilblains: more links for SARS-CoV-2 and less evidence for high interferon type I systemic response
Authors: Didier Bessis, Sophie Trouillet-Assant, Léo-Paul Secco, Nathalie Bardin, Brigitte Blanc, Véronique Blatière, Christine Chable-Bessia, Christophe Delfour, Céline Girard, Jean-Christophe Richard, Nathalie Gros, Vincent Le Moing, Nicolas Molinari, Valérie Pallure, Amandine Pisoni, Nadia Raison-Peyron, Elisa Reynaud, Émilie Schwob, Rémi Pescarmona, Quentin Samaran, Marjolaine Willems, Thierry Vincent, Mircea T. Sofonea, Alexandre Belot, Édouard Tuaillon
Journal: British Journal of Dermatology (2022)

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Fast and noninvasive electronic nose for sniffing out COVID-19 based on exhaled breath-print recognition
Authors: Dian Kesumapramudya Nurputra, Ahmad Kusumaatmaja, Mohamad Saifudin Hakim, Shidiq Nur Hidayat, Trisna Julian, Budi Sumanto, Yodi Mahendradhata, Antonia Morita Iswari Saktiawati, Hutomo Suryo Wasisto, Kuwat Triyana
Journal: npj Digital Medicine (2022)

The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) approach has been widely used to detect the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, instead of using it alone, clinicians often prefer to diagnose the coronavirus disease 2019 (COVID-19) by utilizing a combination of clinical signs and symptoms, laboratory test, imaging measurement (e.g., chest computed tomography scan), and multivariable clinical prediction models, including the electronic nose. Here, we report on the development and use of a low cost, noninvasive method to rapidly sniff out COVID-19 based on a portable electronic nose (GeNose C19) integrating an array of metal oxide semiconductor gas sensors, optimized feature extraction, and machine learning models. This approach was evaluated in profiling tests involving a total of 615 breath samples composed of 333 positive and 282 negative samples. The samples were obtained from 43 positive and 40 negative COVID-19 patients, respectively, and confirmed with RT-qPCR at two hospitals located in the Special Region of Yogyakarta, Indonesia. Four different machine learning algorithms (i.e., linear discriminant analysis, support vector machine, stacked multilayer perceptron, and deep neural network) were utilized to identify the top-performing pattern recognition methods and to obtain a high system detection accuracy (88-95%), sensitivity (86-94%), and specificity (88-95%) levels from the testing datasets. Our results suggest that GeNose C19 can be considered a highly potential breathalyzer for fast COVID-19 screening.
A systems approach towards remote health-monitoring in older adults: Introducing a zero-interaction digital exhaust
Authors: Narayan Schütz, Samuel E. J. Knobel, Angela Botros, Michael Single, Bruno Pais, Valérie Santschi, Daniel Gatica-Perez, Philipp Buluschek, Prabitha Urwyler, Stephan M. Gerber, René M. Müri, Urs P. Mosimann, Hugo Saner, Tobias Nef
Journal: npj Digital Medicine (2022)

Using connected sensing devices to remotely monitor health is a promising way to help transition healthcare from a rather reactive to a more precision medicine oriented proactive approach, which could be particularly relevant in the face of rapid population ageing and the challenges it poses to healthcare systems. Sensor derived digital measures of health, such as digital biomarkers or digital clinical outcome assessments, may be used to monitor health status or the risk of adverse events like falls. Current research around such digital measures has largely focused on exploring the use of few individual measures obtained through mobile devices. However, especially for long-term applications in older adults, this choice of technology may not be ideal and could further add to the digital divide. Moreover, large-scale systems biology approaches, like genomics, have already proven beneficial in precision medicine, making it plausible that the same could also hold for remote-health monitoring. In this context, we introduce and describe a zero-interaction digital exhaust: a set of 1268 digital measures that cover large parts of a person's activity, behavior and physiology. Making this approach more inclusive of older adults, we base this set entirely on contactless, zero-interaction sensing technologies. Applying the resulting digital exhaust to real-world data, we then demonstrate the possibility to create multiple ageing relevant digital clinical outcome assessments. Paired with modern machine learning, we find these assessments to be surprisingly powerful and often on-par with mobile approaches. Lastly, we highlight the possibility to discover novel digital biomarkers based on this large-scale approach.
Qualitative analysis of the impact of atopic dermatitis on caregivers
Authors: Richard W. Kim, Kelly Barta, Wendy S. Begolka, Korey Capozza, Sanaz Eftekhari, Kathryn Tullos, Natalie Tomaszewski, Claire Snell-Rood, Katrina Abuabara
Journal: British Journal of Dermatology (2022)

Dear Editor, Family caregivers play an important role in the wellbeing of individuals with chronic health conditions but can experience psychological, behavioural and physiological effects that can impact their health.1–3 Atopic dermatitis (AD) (also known as eczema) is the most burdensome skin condition worldwide.4 Because it is important to understand the range and nuances of caregiver impact, we sought to qualitatively summarize caregiver perspectives, an area that is understudied compared with patient impact in AD.5 Data are taken from an international survey developed by patient advocacy groups and fielded online in 2019 as part of a US Food and Drug Administration patient‐focused drug development initiative. After scoring the impact of caring for someone with AD, participants were asked to provide additional comments in free‐text form on how AD caregiving has impacted their life. Quantitative results on caregiving are published in a companion research letter (Kim et al., this issue of BJD6). Using an iterative, consensus‐building process, we identified themes and developed a codebook with definitions, typical and atypical exemplars, and exclusions.7 Codes were tested for interrater reliability and then applied in dyads.
The sound of silence: where are the voices of patients in eczema guideline development?
Authors: Korey Capozza, Anne Vastrup, Andrew Proctor, Amanda Roberts, Mario Picozza, Rachael Manion, Cheryl Talent, Marjolaine Hering, Stephanie Merhand, Melanie Funk, Kathryn Z. Tullos, Bernd W.M. Arents
Journal: British Journal of Dermatology (2022)
Genotype–phenotype associations within the Li-Fraumeni spectrum: a report from the German Registry
Authors: Judith Penkert, Farina J. Strüwe, Christina M. Dutzmann, Beate B. Doergeloh, Emilie Montellier, Claire Freycon, Myriam Keymling, Heinz-Peter Schlemmer, Birte Sänger, Beatrice Hoffmann, Tanja Gerasimov, Claudia Blattmann, Sebastian Fetscher, Michael Frühwald, Simone Hettmer, Uwe Kordes, Vita Ridola, Sabine Kroiss Benninger, Angela Mastronuzzi, Sarah Schott, Juliane Nees, Aram Prokop, Antje Redlich, Markus G. Seidel, Stefanie Zimmermann, Kristian W. Pajtler, Stefan M. Pfister, Pierre Hainaut, Christian P. Kratz
Journal: Journal of Hematology & Oncology (2022)

Abstract Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by pathogenic TP53 variants. The condition represents one of the most relevant genetic causes of cancer in children and adults due to its frequency and high cancer risk. The term Li-Fraumeni spectrum reflects the evolving phenotypic variability of the condition. Within this spectrum, patients who meet specific LFS criteria are diagnosed with LFS, while patients who do not meet these criteria are diagnosed with attenuated LFS. To explore genotype–phenotype correlations we analyzed 141 individuals from 94 families with pathogenic TP53 variants registered in the German Cancer Predisposition Syndrome Registry. Twenty-one (22%) families had attenuated LFS and 73 (78%) families met the criteria of LFS. NULL variants occurred in 32 (44%) families with LFS and in two (9.5%) families with attenuated LFS ( P value &lt; 0.01). Kato partially functional variants were present in 10 out of 53 (19%) families without childhood cancer except adrenocortical carcinoma (ACC) versus 0 out of 41 families with childhood cancer other than ACC alone ( P value &lt; 0.01). Our study suggests genotype–phenotype correlations encouraging further analyses.